In order to understand the biochemical basis of morphine tolerance and physical dependence, the interactions between calcium and morphine are being investigated. Calcium has been established to affect the release of neurotransmitters in the brain and evidence has been obtained indicating that calcium antagonizes the analogetic actions of morphine. As an approach to determining the mechanism of this response, the effect of morphine and the opiate peptide, beta-endorphine, on calcium flux will be studied in naive and morphine tolerant-dependent mice and rats. BIBLIOGRAPHIC REFERENCES: Bhargava, H.N. and Way, E.L. (1976): Effects of cholinergic agents on morphine tolerance and physical dependence. Fed. Proc. 35: 580. Harris, R.A., Snell, D., Loh, H.H. and Way, E.L. (1976): Behavioural interactions of apomorphine, clonidine and naloxone: Possible presynaptic involvement. Proc. West. Pharmacol. Soc. 19: 448-451.